Heme oxygenase-1 alleviates allergic airway inflammation by suppressing NF-κB-mediated pyroptosis of bronchial epithelial cells.

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase-1 (HO-1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO-1-mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)-induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO-1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO-1 restrained GSDMD-mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor-Kappa B (NF-κB) p65 RHD domain and thus controlling NF-κB-dependent pyroptosis. These data provide new therapeutic indications for purposing HO-1 to counteract inflammation, which contributes to allergic inflammation control. © 2024 Federation of American Societies for Experimental Biology.

Citation

Jiajia Lv, Yao Zhou, Jing Wang, Yujiao Wu, Qianying Yu, Meng Zhang, Wen Su, Zhiwei Tang, Qun Wu, Min Wu, Zhenwei Xia. Heme oxygenase-1 alleviates allergic airway inflammation by suppressing NF-κB-mediated pyroptosis of bronchial epithelial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2024 Feb 15;38(3):e23472

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PMID: 38329323

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